1 Preamble

This Statistical Analysis Plan (SAP) is written for the PLATCOV trial (registered at ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT05041907).

Data preparation is done in a different R script called data_prep.R. This Markdown script assumes that the data are saved in a .csv file interim_dat.csv in long format. The file interim_dat.csv contains the patient clinical and viral load data with the following column headers:

1.1 Computational setup

##                _                           
## platform       x86_64-apple-darwin17.0     
## arch           x86_64                      
## os             darwin17.0                  
## system         x86_64, darwin17.0          
## status                                     
## major          4                           
## minor          0.2                         
## year           2020                        
## month          06                          
## day            22                          
## svn rev        78730                       
## language       R                           
## version.string R version 4.0.2 (2020-06-22)
## nickname       Taking Off Again
## R version 4.0.2 (2020-06-22)
## Platform: x86_64-apple-darwin17.0 (64-bit)
## Running under: macOS  10.16
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_GB.UTF-8/en_GB.UTF-8/en_GB.UTF-8/C/en_GB.UTF-8/en_GB.UTF-8
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
## [1] brms_2.17.0          Rcpp_1.0.9           plotrix_3.8-2       
## [4] reshape2_1.4.4       RColorBrewer_1.1-2   loo_2.4.1           
## [7] rstan_2.21.2         ggplot2_3.3.5        StanHeaders_2.21.0-7
## 
## loaded via a namespace (and not attached):
##   [1] nlme_3.1-153         matrixStats_0.61.0   xts_0.12.1          
##   [4] threejs_0.3.3        tensorA_0.36.2       tools_4.0.2         
##   [7] backports_1.2.1      bslib_0.3.0          DT_0.19             
##  [10] utf8_1.2.2           R6_2.5.1             DBI_1.1.1           
##  [13] colorspace_2.0-2     withr_2.5.0          tidyselect_1.1.1    
##  [16] gridExtra_2.3        prettyunits_1.1.1    processx_3.7.0      
##  [19] Brobdingnag_1.2-7    emmeans_1.6.3        curl_4.3.2          
##  [22] compiler_4.0.2       cli_3.3.0            shinyjs_2.0.0       
##  [25] sandwich_3.0-1       colourpicker_1.1.0   posterior_1.2.2     
##  [28] sass_0.4.0           scales_1.1.1         dygraphs_1.1.1.6    
##  [31] checkmate_2.0.0      mvtnorm_1.1-2        ggridges_0.5.3      
##  [34] callr_3.7.2          stringr_1.4.0        digest_0.6.29       
##  [37] rmarkdown_2.11       base64enc_0.1-3      pkgconfig_2.0.3     
##  [40] htmltools_0.5.2      fastmap_1.1.0        htmlwidgets_1.5.4   
##  [43] rlang_1.0.4          rstudioapi_0.13      shiny_1.6.0         
##  [46] jquerylib_0.1.4      farver_2.1.0         generics_0.1.0      
##  [49] zoo_1.8-9            jsonlite_1.8.0       gtools_3.9.2        
##  [52] crosstalk_1.1.1      dplyr_1.0.7          distributional_0.3.0
##  [55] inline_0.3.19        magrittr_2.0.3       bayesplot_1.8.1     
##  [58] Matrix_1.3-4         munsell_0.5.0        fansi_1.0.3         
##  [61] abind_1.4-5          lifecycle_1.0.1      multcomp_1.4-17     
##  [64] stringi_1.7.4        yaml_2.2.1           MASS_7.3-54         
##  [67] pkgbuild_1.2.0       plyr_1.8.6           grid_4.0.2          
##  [70] parallel_4.0.2       promises_1.2.0.1     crayon_1.5.1        
##  [73] miniUI_0.1.1.1       lattice_0.20-44      splines_4.0.2       
##  [76] knitr_1.34           ps_1.7.1             pillar_1.8.1        
##  [79] igraph_1.2.6         estimability_1.3     markdown_1.1        
##  [82] shinystan_2.5.0      codetools_0.2-18     stats4_4.0.2        
##  [85] rstantools_2.1.1     glue_1.6.2           evaluate_0.16       
##  [88] V8_3.4.2             RcppParallel_5.1.4   vctrs_0.4.1         
##  [91] httpuv_1.6.3         gtable_0.3.0         purrr_0.3.4         
##  [94] assertthat_0.2.1     xfun_0.26            mime_0.11           
##  [97] xtable_1.8-4         coda_0.19-4          later_1.3.0         
## [100] survival_3.2-13      rsconnect_0.8.24     tibble_3.1.8        
## [103] shinythemes_1.2.0    TH.data_1.0-10       ellipsis_0.3.2      
## [106] bridgesampling_1.1-2
## Warning in checkStrict(calculate_fever_clearance): global variables used: ID,
## Time

2 Overview of data

2.1 Load data

## All negative samples for id: PLT-TH1-128
## PCR database contains data from 236 patients
## we are missing patient PLT-TH1-056
## we are missing patient PLT-BR3-031
## 
##              Favipiravir               Fluoxetine               Ivermectin 
##                       95                       39                       46 
##             Molnupiravir Nirmatrelvir + Ritonavir             Nitazoxanide 
##                       23                       20                        8 
##            No study drug                Regeneron               Remdesivir 
##                       97                       74                       67

2.2 Data summaries

number of patients by analysis

## In the remdesivir analysis there are 131 patients (64 controls and 67 remdesivir)
## In the regeneron analysis there are 158 patients (84 controls and 74 remdesivir)

Display the per protocol matrix

## Number of patients per arm in modified intention to treat analysis
##                Include_mITT
##                 FALSE TRUE
##   No study drug     4   91
##   Regeneron         0   74
##   Remdesivir        0   67
## Number of swabs per protocol per treatment
##                PP_swabs
##                  4  6 18 20
##   No study drug  1  2  0 92
##   Regeneron      0  0  1 73
##   Remdesivir     0  0  0 67
## In the mITT dataset we have 4638 PCR datapoints on 232 patients from 4 sites between 2021-10-02 and 2022-08-24:
## N patients in mITT pop by site:
## 
## br003 th001 th057 th058 
##    16   203     6     7
##                
##                 BA.1 BA.2 BA.4 BA.5 Delta
##   No study drug   13   48    1   19    10
##   Regeneron       15   30    0   16    13
##   Remdesivir      20   37    0    0    10
##                
##                 Delta Omicron
##   No study drug    10      81
##   Regeneron        13      61
##   Remdesivir       10      57
##                
##                 Delta Omicron_G446S Omicron_notG446S
##   No study drug    10            13               68
##   Regeneron        13            15               46
##   Remdesivir       10            20               37
## [1] TRUE
## In the 232 patients, the geometric mean baseline (defined as samples taken within 6 hours of randomisation) viral load was 333936 copies per mL (95 percentile interval from 1736 to 64220513; range from 460 to 79656305)

Summary table

## [1] "Casirivimab\nimdevimab" "Remdesivir"             "No study drug"
## female is 59%
## median age is 28 (IQR: 24-34)
## median time since symptom onset is 2 (IQR: 2-3)
## At least 1 vaccine is 97%
##     25%     50%     75% 
##   59020  374491 2664346
## Censored values up until day 7:
## 
## left none 
##  584 3588
## The proportion censored is 14%
## Variants in mITT database:
## 
##  BA.1  BA.2  BA.4  BA.5 Delta 
##    48   115     1    35    33
## Variants in mITT database by treatment:
##                         
##                          BA.1 BA.2 BA.4 BA.5 Delta
##   Casirivimab\nimdevimab   15   30    0   16    13
##   No study drug            13   48    1   19    10
##   Remdesivir               20   37    0    0    10
Summary of patient characteristics included in the final Remdesivir analysis (n= 232). Age: median (range); baseline viral load (log10 copies per mL: mean (range)); vaccinated: % with any number of doses; number of vaccine doses: median (range); antibody data are from rapid tests done at screening (+ is presence of IgM or IgG band).
Arm n Age Baseline viral load (log10) Number of vaccine doses Antibody+ (%) Male (%) th001 th057 th058 br003
No study drug 64 29.5 (20-50) 5.5 (3-7.9) 3 (0-4) 94 42 52 3 2 7
Remdesivir 67 28 (19-49) 5.5 (2.7-7.4) 3 (0-4) 90 48 54 2 2 9
Summary of patient characteristics included in the final Regeneron analysis (n= 232). Age: median (range); baseline viral load (log10 copies per mL: mean (range)); vaccinated: % with any number of doses; number of vaccine doses: median (range); antibody data are from rapid tests done at screening (+ is presence of IgM or IgG band).
Arm n Age Baseline viral load (log10) Number of vaccine doses Antibody+ (%) Male (%) th001 th058 th057
Casirivimab
imdevimab 74 26 (18-48) 5.7 (3-7.8) 3 (0-5) 88 36 70 3 1
No study drug 84 28.5 (18-46) 5.5 (3-7.9) 3 (2-5) 95 40 79 2 3
Summary of patient characteristics included in the final mITT populations (all patients; n= 232). Age: median (range); baseline viral load (log10 copies per mL: mean (range)); vaccinated: % with any number of doses; number of vaccine doses: median (range); antibody data are from rapid tests done at screening (+ is presence of IgM or IgG band).
Arm n Age Baseline viral load (log10) Number of vaccine doses Antibody+ (%) Male (%) th001 th058 th057 br003
Casirivimab
imdevimab 74 26 (18-48) 5.7 (3-7.8) 3 (0-5) 88 36 70 3 1 0
No study drug 91 29 (18-50) 5.5 (3-7.9) 3 (0-5) 96 38 79 2 3 7
Remdesivir 67 28 (19-49) 5.5 (2.7-7.4) 3 (0-4) 90 48 54 2 2 9

2.3 Summary data plot

This includes all patients in the mITT population with the per protocol swabs.

## Plotting data for 131 individuals
## Plotting data for 158 individuals
## Plotting data for 23 individuals
## Plotting data for 26 individuals
## Plotting data for 73 individuals

## Plotting data for 35 individuals

3 Model fitting

3.1 Simple model using brms

Did this as a sanity check for handwritten models… basically gives the same results

3.2 Full analysis

The primary analysis consists of fitting a sequence of Bayesian hierarchical models to the mITT population (viral load data up until day 7, only patients who did not leave or switch before day 3).

There are a series of model fits, which are combinations of three models:

  • Model 1: vanilla student-t regression with left censoring at 0 and with individual random effects for slope an intercept;
  • Model 2: Linear model with additional RNaseP adjustment (this needs special treatment as we need to subtract the effect of RNaseP for the linear predictions);
  • Model 3: Non-linear model (up and then down) with RNaseP adjustment.

two sets of priors:

  • Weakly informative priors
  • Quasi flat prior (multiply SDs by 10)

and two sets of covariate adjustments:

  • basic covariate adjustment (slope and intercept):
  • Variant (main Greek lineages as defined by WHO)
  • Site
  • Full covariate adjustment (slope and intercept), adding in:
  • Vaccination (number of doses)
  • Age (standardized to have mean=0 and sd=1)
  • Time since symptom onset (days, between 0 and 4)

3.3 Specify priors

get priors

3.4 Prepare models

We make the stan data sets.

## In Remdesivir there are 2620 PCR datapoints and 131 patients
## Analysis dataset contains 131 patients and 2356 datapoints
## In Regeneron there are 3158 PCR datapoints and 158 patients
## Analysis dataset contains 158 patients and 2842 datapoints
## In REGN_Remdesivir_contemporaneous there are 3380 PCR datapoints and 169 patients
## Analysis dataset contains 169 patients and 3040 datapoints
## In Subgroup_Greek there are 3158 PCR datapoints and 158 patients
## Analysis dataset contains 158 patients and 2842 datapoints
## In Subgroup_G446S there are 3158 PCR datapoints and 158 patients
## Analysis dataset contains 158 patients and 2842 datapoints
## In Subgroup_Sublineages there are 3138 PCR datapoints and 157 patients
## Analysis dataset contains 157 patients and 2824 datapoints
## In Full there are 4638 PCR datapoints and 232 patients
## Analysis dataset contains 232 patients and 4172 datapoints
## There are a total of 131 patients in the database with a total of 2356 PCRs analysable
## 14.56% (343 out of 2356) of samples are below LOD
## check stan data formatting:
## There are a total of 158 patients in the database with a total of 2842 PCRs analysable
## 11.65% (331 out of 2842) of samples are below LOD
## check stan data formatting:
## There are a total of 169 patients in the database with a total of 3040 PCRs analysable
## 11.88% (361 out of 3040) of samples are below LOD
## check stan data formatting:
## There are a total of 158 patients in the database with a total of 2842 PCRs analysable
## 11.65% (331 out of 2842) of samples are below LOD
## check stan data formatting:
## There are a total of 158 patients in the database with a total of 2842 PCRs analysable
## 11.65% (331 out of 2842) of samples are below LOD
## check stan data formatting:
## There are a total of 157 patients in the database with a total of 2824 PCRs analysable
## 11.44% (323 out of 2824) of samples are below LOD
## check stan data formatting:
## There are a total of 232 patients in the database with a total of 4172 PCRs analysable
## 14% (584 out of 4172) of samples are below LOD
## check stan data formatting:
## There are a total of 158 patients in the database with a total of 2842 PCRs analysable
## 11.65% (331 out of 2842) of samples are below LOD
## check stan data formatting:
## There are a total of 158 patients in the database with a total of 2842 PCRs analysable
## 11.65% (331 out of 2842) of samples are below LOD
## check stan data formatting:
## There are a total of 157 patients in the database with a total of 2824 PCRs analysable
## 11.44% (323 out of 2824) of samples are below LOD
## check stan data formatting:

3.5 Setup model runs

List all parameters settings for the model fitting:

## We are running all models with 4 chains and 4000 samples for each chain, discarding 2000 for burn-in and thining every 8, thus giving a total of 1000 posterior samples per model.

All model fitting is run on a cluster using run_models.R (bmrc.sh provides bash commands)

Load model fits

4 Results

main models

4.1 Remdesivir

Plot the remdesivir versus no study drug output

##  2.5%   10%   50%   90% 97.5% 
##    18    26    42    62    73
## The model estimated population mean clearance half-life is 24.9 (95% CI 18.8-33.2)

## In No study drug the median clearance half life was 18 (range 3.6 to 46.7)
## In Remdesivir the median clearance half life was 12.8 (range 4.8 to 50)
## The following `from` values were not present in `x`: Age_scaled, Antibody_test, Symptom_onset, N_dose
## The following `from` values were not present in `x`: Age_scaled, Antibody_test, Symptom_onset, N_dose
##        
##         Subvariant BA.1 Subvariant BA.2 Subvariant BA.4 Subvariant BA.5
##   2.5%             0.50            0.97            0.36            0.29
##   10%              0.57            1.12            0.54            0.37
##   50%              0.77            1.48            0.98            0.69
##   90%              1.06            1.92            1.95            1.30
##   97.5%            1.24            2.21            2.78            1.71
##        
##         Siteth057 Siteth058 Sitebr003
##   2.5%       0.27      0.30      0.39
##   10%        0.34      0.36      0.46
##   50%        0.54      0.58      0.63
##   90%        0.84      0.92      0.87
##   97.5%      1.12      1.15      1.03
##        
##         Subvariant BA.1 Subvariant BA.2 Subvariant BA.4 Subvariant BA.5
##   2.5%             0.93            1.07            0.35            0.60
##   10%              1.04            1.18            0.52            0.83
##   50%              1.27            1.43            0.98            1.35
##   90%              1.58            1.71            1.89            2.16
##   97.5%            1.76            1.88            2.72            2.75
##        
##         Siteth057 Siteth058 Sitebr003
##   2.5%       0.84      0.79      0.78
##   10%        0.99      0.93      0.87
##   50%        1.34      1.28      1.07
##   90%        1.83      1.76      1.32
##   97.5%      2.10      2.15      1.45

4.2 Regeneron

Same effect in all variants assumed

##  2.5%   10%   50%   90% 97.5% 
##     8    13    25    39    46
## The model estimated population mean clearance half-life is 17 (95% CI 13.6-21)

## In Casirivimab
## imdevimab the median clearance half life was 12.7 (range 5.8 to 27.7)
## In No study drug the median clearance half life was 16.2 (range 4.2 to 40.5)
## The following `from` values were not present in `x`: Age_scaled, Antibody_test, Symptom_onset, N_dose
## The following `from` values were not present in `x`: Age_scaled, Antibody_test, Symptom_onset, N_dose
##        
##         Subvariant BA.1 Subvariant BA.2 Subvariant BA.4 Subvariant BA.5
##   2.5%             0.49            0.85            0.39            0.57
##   10%              0.58            0.98            0.52            0.68
##   50%              0.80            1.29            0.95            0.91
##   90%              1.08            1.68            1.61            1.20
##   97.5%            1.26            1.89            2.25            1.41
##        
##         Siteth057 Siteth058 Sitebr003
##   2.5%       0.40      0.40      0.38
##   10%        0.50      0.52      0.54
##   50%        0.80      0.80      1.01
##   90%        1.27      1.34      1.90
##   97.5%      1.61      1.67      2.59
##        
##         Subvariant BA.1 Subvariant BA.2 Subvariant BA.4 Subvariant BA.5
##   2.5%             0.77            0.76            0.81            0.83
##   10%              0.85            0.82            1.05            0.92
##   50%              1.01            0.96            1.62            1.08
##   90%              1.21            1.10            2.46            1.27
##   97.5%            1.34            1.20            3.04            1.39
##        
##         Siteth057 Siteth058 Sitebr003
##   2.5%       0.69      0.98      0.37
##   10%        0.81      1.15      0.51
##   50%        1.11      1.51      1.01
##   90%        1.48      1.97      2.02
##   97.5%      1.74      2.25      3.06

4.3 Both interventions together

Up until 10 June in Thai sites (where regeneron was available)

##  2.5%   10%   50%   90% 97.5% 
##   -49   -40    34    92   121
## The model estimated population mean clearance half-life is 22.6 (95% CI 17.7-28.8)

## In Casirivimab
## imdevimab the median clearance half life was 12.9 (range 6.1 to 31)
## In No study drug the median clearance half life was 17.6 (range 3.8 to 42.7)
## In Remdesivir the median clearance half life was 13 (range 4.8 to 45.7)
## probability that remdesivir is less than REGN in Delta:
## [1] 0.942
## probability that remdesivir is greater than REGN in Omicron:
## [1] 0.933

4.3.1 All data combined

## Ranking probabilities:
##    
##     Remdesivir Casirivimab\nimdevimab (Delta) Casirivimab\nimdevimab (Omicron)
##   1         90                             17                              893
##   2        812                             86                              102
##   3         98                            897                                5

## 
##   No study drug (Delta) No study drug (Omicron)            REGN (Delta) 
##                      10                      81                      13 
##          REGN (Omicron)              Remdesivir 
##                      61                      67
## The model estimated population mean clearance half-life is 22.1 (95% CI 17.4-27.3)

## In No study drug (Delta) the median clearance half life was 21.8 (range 14.3 to 31.3)
## In No study drug (Omicron) the median clearance half life was 16.5 (range 3.9 to 43.1)
## In REGN (Delta) the median clearance half life was 12.4 (range 6.3 to 20)
## In REGN (Omicron) the median clearance half life was 13 (range 5.7 to 30.3)
## In Remdesivir the median clearance half life was 12.7 (range 4.9 to 45)
## The following `from` values were not present in `x`: Antibody_test, N_dose
## The following `from` values were not present in `x`: Antibody_test, N_dose
##        
##         Subvariant BA.1 Subvariant BA.2 Subvariant BA.4 Subvariant BA.5
##   2.5%             0.66            1.04            0.42            0.57
##   10%              0.76            1.19            0.53            0.67
##   50%              0.97            1.47            0.93            0.88
##   90%              1.29            1.84            1.62            1.12
##   97.5%            1.49            2.03            2.34            1.29
##        
##         Siteth057 Siteth058 Sitebr003  Age Days since\nsymptom onset
##   2.5%       0.31      0.35      0.45 0.97                      0.54
##   10%        0.39      0.45      0.52 1.01                      0.58
##   50%        0.59      0.67      0.71 1.10                      0.65
##   90%        0.86      0.98      0.96 1.20                      0.72
##   97.5%      1.07      1.17      1.14 1.25                      0.76
##        
##         Subvariant BA.1 Subvariant BA.2 Subvariant BA.4 Subvariant BA.5
##   2.5%             0.85            0.98            0.90            1.05
##   10%              0.94            1.05            1.14            1.14
##   50%              1.11            1.23            1.79            1.37
##   90%              1.33            1.45            2.81            1.65
##   97.5%            1.46            1.58            3.60            1.82
##        
##         Siteth057 Siteth058 Sitebr003  Age Days since\nsymptom onset
##   2.5%       0.88      1.00      0.80 0.90                      0.93
##   10%        1.00      1.11      0.88 0.91                      0.97
##   50%        1.28      1.41      1.06 0.96                      1.03
##   90%        1.66      1.79      1.26 1.00                      1.10
##   97.5%      1.95      2.02      1.41 1.02                      1.14

4.4 Regeneron subgroups

4.4.1 Greek variant

## 
##   Casirivimab\nimdevimab (Delta) Casirivimab\nimdevimab (Omicron) 
##                               13                               61 
##            No study drug (Delta)          No study drug (Omicron) 
##                               10                               81 
##                       Remdesivir 
##                               67
## The model estimated population mean clearance half-life is 19.6 (95% CI 14.5-26.1)

## In Casirivimab
## imdevimab (Delta) the median clearance half life was 12.3 (range 6.2 to 19.4)
## In Casirivimab
## imdevimab (Omicron) the median clearance half life was 13.1 (range 5.8 to 27.9)
## In No study drug (Delta) the median clearance half life was 20.8 (range 14.1 to 29)
## In No study drug (Omicron) the median clearance half life was 15.7 (range 4.2 to 40.3)

4.4.2 G446S mutation

## 
##     Casirivimab\nimdevimab (Delta)     Casirivimab\nimdevimab (G446S) 
##                                 13                                 15 
## Casirivimab\nimdevimab (not G446S)              No study drug (Delta) 
##                                 46                                 10 
##              No study drug (G446S)          No study drug (not G446S) 
##                                 13                                 68 
##                         Remdesivir 
##                                 67
## The model estimated population mean clearance half-life is 18.8 (95% CI 14.2-24.5)

## In Casirivimab
## imdevimab (Delta) the median clearance half life was 12.3 (range 6.3 to 19.2)
## In Casirivimab
## imdevimab (G446S) the median clearance half life was 11.8 (range 7 to 27.8)
## In Casirivimab
## imdevimab (not G446S) the median clearance half life was 13.3 (range 5.8 to 24.2)
## In No study drug (Delta) the median clearance half life was 20.4 (range 13.8 to 29.2)
## In No study drug (G446S) the median clearance half life was 13.5 (range 7.5 to 23.2)
## In No study drug (not G446S) the median clearance half life was 16.5 (range 4.2 to 40.3)

4.5 Sublineages subgroup analysis

## 
##  Casirivimab\nimdevimab (BA.1)  Casirivimab\nimdevimab (BA.2) 
##                             15                             30 
##  Casirivimab\nimdevimab (BA.5) Casirivimab\nimdevimab (Delta) 
##                             16                             13 
##           No study drug (BA.1)           No study drug (BA.2) 
##                             13                             48 
##           No study drug (BA.5)          No study drug (Delta) 
##                             20                             10 
##                     Remdesivir 
##                             67
## The model estimated population mean clearance half-life is 18.6 (95% CI 14.2-24)

## In Casirivimab
## imdevimab (BA.1) the median clearance half life was 11.8 (range 7 to 28.2)
## In Casirivimab
## imdevimab (BA.2) the median clearance half life was 13.6 (range 6.3 to 24.9)
## In Casirivimab
## imdevimab (BA.5) the median clearance half life was 11.4 (range 5.7 to 21.8)
## In Casirivimab
## imdevimab (Delta) the median clearance half life was 12.2 (range 6.2 to 19.6)
## In No study drug (BA.1) the median clearance half life was 13.5 (range 7.5 to 23)
## In No study drug (BA.2) the median clearance half life was 18.1 (range 4.3 to 41.1)
## In No study drug (BA.5) the median clearance half life was 14.2 (range 7.9 to 28)
## In No study drug (Delta) the median clearance half life was 20.1 (range 13.9 to 28.4)

4.5.1 Make main figure

##                                            2.5% 10% 50% 90% 97.5%
## All variants\n(n=67 vs n=64)                 18  26  42  62    73
## All variants\n(n=74 vs n=84)                  8  13  25  39    46
## Delta\n(n=13 vs n=10)                        10  24  58  98   120
## Omicron\n(n=61 vs n=74)                       3   7  20  33    43
## Delta\n(n=13 vs n=10)                         8  22  50  86   109
## Omicron\nG446S mutated\n(n=15 vs n=11)      -21 -11   8  39    59
## Omicron\nnot G446S mutated\n(n=46 vs n=63)    3   9  23  39    49

4.6 Slope fits

## 
## Call:
## lm(formula = slope ~ Trt, data = plat_summary)
## 
## Residuals:
##      Min       1Q   Median       3Q      Max 
## -1.39086 -0.11783  0.04102  0.18806  0.47932 
## 
## Coefficients:
##               Estimate Std. Error t value Pr(>|t|)    
## (Intercept)   -0.47212    0.02610 -18.090  < 2e-16 ***
## TrtRegeneron  -0.11932    0.03897  -3.062  0.00246 ** 
## TrtRemdesivir -0.16649    0.04008  -4.154 4.62e-05 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 0.249 on 229 degrees of freedom
## Multiple R-squared:  0.0773, Adjusted R-squared:  0.06924 
## F-statistic: 9.593 on 2 and 229 DF,  p-value: 9.984e-05

## 
##  Pearson's product-moment correlation
## 
## data:  plat_summary$slope[ind] and plat_summary$clearance_time[ind]
## t = 0.68342, df = 127, p-value = 0.4956
## alternative hypothesis: true correlation is not equal to 0
## 95 percent confidence interval:
##  -0.1135097  0.2309701
## sample estimates:
##        cor 
## 0.06053241